SINGLE FIBER ANALYSIS OF DENERVATED AND AGING MUSCLE

拟议研究的广泛目标是在单个全肌纤维水平上确定在衰老和长期失神经肌肉中观察到的反应背后的细胞和分子事件。具体来说，这些包括1)去神经支配后卫星细胞激活的时间过程和地形，2)衰老和去神经支配肌肉中与现有肌纤维一起形成新肌纤维，3)在7个月的去神经支配肌肉中发生的不寻常的核团块现象，4)从组织水平的分子分析来看，重要基因的表达时间和形态在肌纤维对去神经支配和衰老的反应中起重要作用。麦克伦南博士的宿主实验室研究了哺乳动物胎儿的肌管形成，以及组织中肌肉再生的分子方面。拟议的实验将把麦克伦南博士的分子专业知识与申请人的形态学和实验专业知识结合起来，并将麦克伦南博士在细胞水平上研究产前肌肉发生的经验与申请人在生命的另一端研究新生肌肉发生的经验结合起来。这项拟议的研究是一个项目的一部分，该项目旨在设计增强衰老和失神经肌肉恢复能力的方法。

The broad goal of the proposed research is to determine at the single whole muscle fiber level cellular and molecular events that underlie reactions that have been observed in both aging and long-term denervated muscle. Specifically, these include 1) the time course and topography of satellite cell activation after denervation, 2) the formation of new muscle fibers alongside existing ones in both aging and denervated muscle, 3) an unusual nuclear clumping phenomenon that occurs in 7-month denervated muscle, and 4) the time course and topography of expression of important genes that from tissue-level molecular analysis appear to play an important role in the reactions of muscle fibers to both denervation and aging. The host laboratory of Dr. McLennan has studied myotube formation in the mammalian fetus, as well as molecular aspects of muscle regeneration in tissues. The proposed experiments will combine Dr. McLennan's molecular expertise with the applicant's morphological and experimental expertise, and it will bring together Dr. McLennan's experience in studying prenatal myogenesis at the cellular level with that of the applicant, who is studying neomyogenesis at the other end of the life span. The proposed research is part of a project designed to devise ways of enhancing the restorative ability of aging and denervated muscles.